This 5-year, two-site R0l proposal, based in New York and in Pittsburgh, is a competitive renewal of a high-risk study of the familial transmission of early-onset suicidal behavior. By the end of the first funding period, we will have recruited the offspring of two groups of probands-approximately 334 offspring of 167 mood disordered suicide attempters and a comparison group of 168 offspring of 83 mood disordered non-attempters. Probands, biological offspring over the age of 10, and the biological co-parent were characterized as to psychopathology, suicide attempt history, tendency to impulsive aggression and family environment, and were genotyped with polymorphic markers for serotonin pathway genes. Results of cross-sectional analyses indicate clear evidence of the familial transmission of suicidal acts and its relationship to both transmission of mood disorders and other psychopathology such as aggression/impulsivity and family adversity including sexual abuse. Offspring of multiplex families have the highest risk for attempt and earliest age of onset. We now propose to follow up offspring, as they move through the age of risk for a first suicide attempt. Probands will also be reassessed, as their clinical status can affect offspring outcome. Subjects will be re-assessed with respect to psychopathology, impulsive aggression, and suicidal behavior. In addition, laboratory-based measures of impulsivity and executive function, and more detailed assessment of trauma history and family adversity will be obtained. Direct sequencing of candidate genes will be conducted in families multiplex for suicide attempt. The prospective tracking of offspring will permit detection of the evolution of psychopathology and development of a predictive and explanatory model for the familial transmission of suicidal behavior. This study should lead to an empirical basis for the prevention and treatment of suicidal behavior.